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Background: NUP98 gene fusions in acute myeloid leukemia (AML) have recently attracted much interest. Despite substantial research illuminating the roles of NUP98 fusions in the course of AML, their impacts on the outcome of patients with AML should be explored in more detail. As a result, this meta-analysis was designed to provide further light on the prognostic implications of NUP98 fusions in AML. Methods: We completed an extensive search in PubMed, Scopus, and Web of Science to identify papers evaluating the prognostic effects of NUP98 rearrangements in patients with AML until August 22, 2022. In total, 15 publications with 6142 participants fulfilled the requirements for the current meta-analysis. All the qualified studies were examined for information regarding HRs and 95% confidence interval (95%CI) for overall survival (OS) and event-free survival (EFS). In addition, we utilized Comprehensive Meta-analysis software version 2 (CMA2) for calculating pooled HRs and 95% CI. Results: Our analyses for NUP98-NSD1 indicated that this fusion could significantly impact the outcome of patients with AML (pooled HR: 2.84; 95% CI: 2.49-3.24, P=0.000). Additionally, we observed a strong correlation between NUP98-KDM5A rearrangement and poor prognosis in AML (pooled HR: 2.65; 95% CI: 2.5-2.81; P=0.000). A subgroup analysis also showed that the NUP98-NSD1 and FLT3-ITD together confer a poor prognostic effect (pooled HR: 2.60, 95% CI: 1.61-4.18; P=0.000). Conclusions: NUP98 fusions could significantly impact the outcome of patients with AML. The use of these fusions as prognostic indicators in AML seems rational. [ABSTRACT FROM AUTHOR]

Background: The current study intends to assess the impact of oral selenium intake on anti-Tg antibody in individuals with autoimmune hypothyroidism. Methods: In this double-blinded randomized controlled trial, two groups of 72 autoimmune hypothyroid patients were randomly assigned; One group received levothyroxine (LT4) and oral selenium and the other group was given placebo with LT4. Anti-Tg antibody, free T4, anti-TPO antibody, and TSH were identified in both groups before the treatment and also 3 months after treatment and analysis of data was done by SPSS software. Results: After the intervention, the average amount of anti-Tg antibody decreased in both of the groups, and this decrease was noticeably greater in the intervention group (P = 0.03). In the intervention group, the TSH level decreased after the intervention (p < 0.05), and the free T4 level increased after the intervention (p < 0.05); the changes in these two variables were statistically significant. Conclusion: Consumption of selenium, compared to placebo, in patients with autoimmune hypothyroidism drastically reduces the level of anti-Tg antibody, and it significantly increases the free T4 level. Also, there is a greater decrease in the level of TSH compared to the control group. [ABSTRACT FROM AUTHOR]

Background: Although genetic mutations in additional sex-combs-like 1 (ASXL1) are prevalent in acute myeloid leukemia (AML), their exact impact on the AML prognosis remains uncertain. Hence, the present article was carried out to explore the prognostic importance of ASXL1 mutations in AML. Methods: We thoroughly searched electronic scientific databases to find eligible papers. Twenty-seven studies with an overall number of 8,953 participants were selected for the current systematic review. The hazard ratio (HR) and 95% confidence interval (CI) for overall survival (OS), event-free survival (EFS), and relapse-free survival (RFS) were extracted from all studies with multivariate or univariate analysis. Pooled HRs and pvalues were also calculated as a part of our work. Results: The pooled HR for OS in multivariable analysis indicated that ASXL1 significantly diminished survival in AML patients (pooled HR: 1.67; 95% CI: 1.342-2.091). Conclusions: ASXL1 mutations may confer a poor prognosis in AML. Hence, they may be regarded as potential prognostic factors. However, more detailed studies with different ASXL1 mutations are suggested to shed light on this issue. [ABSTRACT FROM AUTHOR]

Background: Autophagy is a pathway for the degradation of cytoplasmic components, which plays an essential role in various cellular and physiological processes, including cell renewal and survival, and immune responses. While recent studies have shown that they can play a role in cancer treatment, the precise mechanisms of autophagy in leukemogenesis are not fully understood. We have assessed the expression levels of LC3 and BECLIN1 as two crucial autophagy mediators in patients with leukemia. Methods: This cross-sectional study was performed on bone marrow or peripheral blood samples of 61 leukemia patients (24 AML, 20 ALL, and 17 CML) and compared to 18 healthy controls. Real-time PCR was used to quantitate gene expression. SPSS statistics 16.0 and Graph Pad Prism 8.4.2 software were applied for statistical analysis. Results: While BECLIN1 expression was significantly lower in AML, ALL, and CML patients as compared to the control group (p < 0.05), LC3 showed significantly different expression only in the AML patients (P= 0.03). There was no significant correlation between the expression levels of BECLIN1 with LC3 (p> 0.05). Whilst the AML LC3high group had a significantly lower lymphocyte count (P= 0.023), the AML BECLIN1low group had a significantly higher MPV levels (P= 0.044). Furthermore, ALL LC3high group indicated a significantly lower HCT count (P= 0.017). Conclusion: Significant changes in the expression levels of BECLINI and LC3 in hematologic malignancies may indicate a possible role for autophagy in their pathogenesis. However, further studies are warranted to confirm these findings. [ABSTRACT FROM AUTHOR]

Background & Objective: Chronic myeloid leukemia (CML) is a myeloproliferative disorder caused by an aberrant BCR-ABL fusion protein. Imatinib mesylate (IM) is a tyrosine kinase inhibitor that induces clinical remissions in chronic-phase CML patients. The T315I mutation at the gatekeeper residues of BCR-ABL confers resistance to both IM and second-generation TKIs, including dasatinib and nilotinib. Our objective was to determine the prevalence of T315I mutation between two groups of CML patients before and during Imatinib treatment in North-East of Iran. Materials & Methods: This study was conducted on 100 newly diagnosed cases of CML (before commencing IM treatment) and 25 IM-resistant CML patients. PCRRFLP, ASO-PCR, and direct sequencing were performed to detect T315I mutations. Results: The median age of newly-diagnosed and IM-resistant patients was 48±14 and 50±12.3 years, respectively. Males/Females ratio was 1 and 1.08 for newly diagnosed and IM-resistant patients, respectively. There was no significant difference regarding the age and sex between the two groups. During the study, T315I mutational analysis was performed for all 125 patients. The prevalence of T315I mutation was 0% and 4% for newly-diagnosed and IM-resistant patients, respectively. T315I mutation was not detected before IM administration, although it was detected in 1(4%) among resistant patients who were at least 6-months on IM treatment. Conclusion: These observations suggest that T315I mutation may be categorized as secondary resistance and induce clonal expansion due to BCR/ABL instability. Hence, BCR-ABL mutations [ABSTRACT FROM AUTHOR]

Background: Papillomatosis is a known histopathologic pattern usually seen in human papillomavirus (HPV) infection and verruca vulgaris is the typical example. This pattern is also detected in some other benign cutaneous lesions such as nevus sebaceous (NS), seborrheic keratosis (SK), trichilemmoma (TL) and inverted follicular keratosis (IFK). The association between papillomatous lesions and HPV infection is questionable. Objective: The objective of this study was to investigate the presence of HPV deoxyribonucleic acid (DNA) in non-genital benign papillomatous skin lesions (NS, SK, TL and IFK) by polymerase chain reaction (PCR). Materials and Methods: A total of 100 specimens of non-genital NS, SK, TL and IFK were retrieved from archives of Dermatopathology Department of Razi Hospital, between 2003 and 2010. The conventional PCR using consensus GP5+/GP6+ primer and hydroxymethylbilane synthase gene as inner control was performed. Results: PCR for HPV DNA revealed no positive results in any of 28 seborrheic keratosis (SK), 28 nevus sebaceous (NS), 28 inverted follicular keratosis (IFK) and 13 trichilemmoma (TL) studied specimens. Conclusion: Papillomatosis is usually a characteristic pattern of HPV infection. However, we found no association between HPV infection and non-genital benign papillomatous lesions.

The basic pathogenic step in the process of tumor growth, invasion and metastasis is tumor-induced angiogenesis. The aim of this study was to evaluate the angiogenesis in colorectal carcinoma by microvascular density (MVD) determination with IHC (immunohistochemistry) method and to determine if and how angiogenesis correlates with clinicopathologic parameters. Sixty two archival, paraffin embedded tissue samples of colorectal carcinoma from Omid Hospital (Mashhad, Islamic republic of Iran) were selected. Microvessels were identified immunohistochemically, using monoclonal CD34 antibody. Two investigators examined the microvessel density then the median value of MVD was determined and correlated with clinicopathologic parameters. Tumor-induced angiogenesis of colorectal carcinoma statistically correlated with histological tumor grade (P=0.000). There was no significant correlation between intratumoral microvessel density and sex and age of patients, localization, and stage and histologicalal tumor type (P > 0.1). Intratumoral microvessel density quantification in histologic specimens of colorectal carcinoma reflects the grade of tumors and may be a useful additional prognostic factor.

Endothelial dysfunction is thought to be a central pathogenic feature in preeclampsia on the basis of elevated adhesion molecules. Soluble forms of these molecules can be detected in plasma, and their concentrations are thought to reflect the degree of activation of a particular cell type. The aim of the present study was to compare the levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) in sera of normal and preeclamptic pregnancies. A cross-sectional study was conducted to determine the plasma concentrations of sVCAM-1 in peripheral blood obtained from normal pregnant women (n=40), mild preeclampsia (n=37) and severe preeclampsia (n=38). Concentrations of soluble adhesion molecule was determined with enzyme-linked immunosorbant assay (ELISA). Serum concentration of sVCAM-1 was significantly higher in severe preeclampsia (P

Background: Thalassemia is a common hemoglobin disorder in Iran and one of the major public health problems. Although blood transfusions are lifesavers for thalassemia patients, they may be associated with some complications especially erythrocyte alloimmunization. The purpose of this study was to investigate the prevalence of red blood cell alloantibodies and to determine types of these antibodies among multiple-transfused thalassemic patients. Materials and Methods: A total of 313 thalassemia patients in the northeast of Iran, who received regular blood transfusion, were included in this study. Screening of antibodies was performed on fresh serum of all patients and then antibodies were identified in patients′ serum that had positive antibody screening test using a panel of recognized blood group antigens. Results: We identified 12 alloantibodies in 9 patients (2.87%) that all were against Rhesus (Rh) blood group antigens (D, C, E). Three patients developed 2 antibodies, and others had one antibody. The most common alloantibodies were Anti-D (88.88%) and followed by Anti-C and Anti-E. Higher frequency of alloimmunization was observed in female, Rh negative and splenectomized patients. Conclusion: This study showed that evaluation of the packed cells for Rh (C, E) from the start of transfusion can be helpful in decreasing the rate of alloantibody synthesis.

This study was conducted to assess the effect of oral calcitriol on glucose metabolism in patients on hemodialysis (HD). A total of 27 patients on HD at the Mashhad University of Medical Sciences, Iran, none of whom had received calcitriol or had history of diabetes, were selected. The patients were randomly divided into two groups; Group I: patients who received oral calcitriol for eight weeks and, Group II: patients who received placebo. In all cases, levels of fasting glucose, insulin, lipid profile, calcium, phosphorous, parathormone (PTH), HbA1C and blood sugar after administration of 75 grams of glucose, insulin resistance and beta cell function were measured, before and after the treatment period. The two sets of results were then compared with one another. In Group l patients, the levels of the parameters studied before and after the study period were as follows: blood sugar after 75 grams of glucose (88.67 ± 8.68 versus 99.83 ± 34.42 mg/dL, p = 0.045), HOMA-IR (2.05 ± 1.42 versus 2.42 ± 1.33, p = 0.035), HbA1C (5.99 ± 1.00 versus 6.14 ± 1.19, p = < 0.001), total cholesterol (153.3 ± 43.80 mg/dL versus 157.0 ± 52.62, p = 0.037) and triglycerides (175.30 ± 99.65 versus 214.9 ± 117.7 mg/dL, p = 0.036). Thus, there was a significant decrease after the study period. In Group II, fasting blood sugar (110.7 ± 26.12 versus 81.14 ± 13.31 mg/dL, p = 0.002), HbA1C (6.99 ± 1.44 versus 6.17 ± 1.66, p = 0.004) and HOMA-IR (5.85 ± 5.11 versus 3.20 ± 2.39, p = 0.036) significantly increased and beta cell function significantly decreased (149.5 ± 90.57 versus 355.7 ± 299.3, p = 0.032) after the study period. In conclusion, our results show that vitamin D has a significant influence on glucose metabolism. Similar studies on larger sample size are required to confirm this observation.

Background: The B-cell-specific Moloney murine leukemia virus integration site1 (BMI-1) is one of the famous members of the Polycomb ring finger group, which plays a crucial role in the gene transcription regulation through histone changes. Hence, it is believed to be necessary to further clarify the effects of the BMI-1 clinical. Method: This cross-sectional study was conducted on 70 acute myeloid leukemia (AML), 70 chronic myeloid leukemia (CML), and 20 healthy individuals, as the control group. We used real-time quantitative polymerase chain reaction in order to assess the BMI-1 level expression and its effect on prognosis in AML patients in the Molecular Pathology Research Center. Results: The results of the present work indicated that the BMI-1 overexpression was significantly higher in the AML and CML patients compared with that in the healthy controls (P < 0.001). Furthermore, a significant relationship was observed between the BMI-1 overexpression and poor prognosis in the AML patients (Hazard ratio=1.749, P < 0.001, 95% confidence interval = 1.31-2.32). Additionally, BMI-1 high was found in chronic and blastic phase in the CML patients (P < 0.001). Conclusion: We concluded that investigation of BMI-1 gene expression pattern will be conducive to the prognosis and treatment of myeloid leukemia. [ABSTRACT FROM AUTHOR]

Background and objectives: Fanconi anemia (FA) is an autosomal recessive disorder that usually manifest in forms of pancytopenia, hyperpigmentation, and skeletal complications. Mutation in the DNA repair regulatory genes is associated with the development of FA. Examination of chromosomal breakages when chromosomes are exposed to cross-linking agents is a common method of FA diagnosis. This study aimed to evaluate the prevalence and characteristics of patients with FA in Mashhad, northeast of Iran. Methods: In this study, we evaluated 312 suspected FA patients who had been referred to the laboratory of Ghaem Hospital during 2014-2020. The mitomycin C method was used to identify FA-positive subjects. Results: After the examinations, 84 patients (26.9%) were cytogenetically positive for FA. Of 84 patients, 48 (57.1%) were male and 36 (42.9%) were female. Thumb abnormality was the most common congenital anomaly (43.2%). Conclusion: Based on the findings, males are more susceptible to FA, and thumb abnormality is the most common congenital anomaly associated with FA. Combination of clinical manifestations and genetic susceptibility in patients may contribute to a more accurate diagnosis. [ABSTRACT FROM AUTHOR]

Background: Chromosomal aberrations which occur in different hematologic malignancies are believed to be highly applicable for identifying the prognosis and treatment protocols. We conducted the present study to investigate the chromosomal and molecular abnormalities in bone marrow of acute myeloid leukemia (AML), acute lymphoid leukemia (ALL), and myelodysplastic syndrome patients. Method: We performed this cross-sectional study in molecular pathology and cancer research center of Mashhad University of Medical Sciences (MUMS), during 2017-2019; the total number of our cases was 252. We did all the molecular and cytogenetic tests on these patients. SPSS V.16 software was utilized for the analysis of our data. Results: In this research, the ALL patients were meaningfully younger than AML ones. There were significant associations between karyotype patterns and types of malignancy; normal diploid was more frequent in myelodysplastic syndrome (P<0.05). Among numerical abnormalities, trisomy 3 and monosomy 14 were the most prevalent ones. Conclusion: The results of similar studies from different areas with different ethnics would help to identify new parameters for prognosis determination. Cytogenetic analysis is highly applicable for leukemia diagnosis and prognosis. [ABSTRACT FROM AUTHOR]

Background: Acute lymphoblastic leukemia (ALL) is a highly heterogeneous malignancy that accounts for nearly 75% of leukemias in children. While the exact mechanism of ALL is not fully understood, some genetic variants have been implicated as associated with ALL susceptibility. The association between some genetic variants in miRNA genes and ALL risk has been described previously. A previous study suggested that mir-612 rs12803915 G> A may be associated with pediatric ALL risk. High-resolution melting (HRM) analysis is a reliable method that can be applied for polymorphism detection. Methods: This retrospective study was performed on 100 B-ALL patients (52 males and 48 females; age 4.6 ± 3.2 years) and 105 age- and sex-matched healthy controls (48 males and 57 females; age 5.1 ± 3 years). We used HRM to identify mir-612 rs12803915 genotypes. Sanger sequencing was applied to validate the HRM results. Results: High resolution melting analysis was used to genotype the mir-612 rs12803915 polymorphism. We found no association between rs12803915 allele A and B-ALL risk in any inheritance models (p> 0.05). Conclusions: HRM is a suitable method to detect SNP rs12803915 in the mir-612 gene; however, we found no significant association between the rs12803915 polymorphism and ALL risk. [ABSTRACT FROM AUTHOR]

Objective(s): Adult T-cell leukemia/lymphoma (ATLL) is an aggressive lymphoid malignancy with low survival rate and distinct geographical distribution. In search for novel chemotherapeutics against ATLL, we investigated the combinatorial effects of parthenolide, a sesquiterpene lactone with valuable pharmaceutical activities, and arsenic trioxide (ATO) in vitro. Materials and Methods: MT2 cells, an ATLL cell line, were treated with increasing concentrations of parthenolide (1.25, 2.5, and 5 μg/ml) and ATO (2, 4, 8, and 16 μM) to determine their IC50. Then, cells were treated with a combination of sub-IC50 concentrations of parthenolide (1 μg/ml) and ATO (2 μM) for 72 hr. Cell viability and cell cycle changes were assessed by Alamar blue and PI staining, respectively. To understand the mechanisms responsible for observed effects, expression of CD44, NF-κB (REL-A), BMI-1, and C-MYC were investigated by real-time PCR. Results: Assessment of cell viability indicated that parthenolide significantly increased the toxicity of ATO, as confirmed by accumulation of MT2 cells in the sub G1 phase of the cell cycle. Moreover, molecular analysis revealed significant down-regulation of CD44, NF-κB (REL-A), BMI-1, and C-MYC upon combinatorial administration of parthenolide and ATO in comparison with relevant controls. Conclusion: Taken together, present results showed that parthenolide significantly enhanced the toxicity of ATO in MT2 cells. Therefore, the future possible clinical impact of our study could be combinatorial use of parthenolide and ATO as a novel and more effective approach for ATLL. [ABSTRACT FROM AUTHOR]